Pharmacometabonomics, as an emerging branch of system biology, has been increasingly used in personalized medicine and showed broad prospects. By means of metabonomics, the complicated and detailed metabolic profile of the patient is described, thus providing more detailed description of the disease phenotype. With this understanding, response of different individuals to the drugs are predicted or evaluated through inherent genetic information of the individual combined with the environmental factors. As a result, appropriate drugs and dosage are chosen, which greatly promotes the realization of the individualized therapy goals. This article describes the emerging field of pharmacometabonomics, and the research results of personalized medicine based on the pharmacometabonomics in recent years are reviewed in detail.
Humans ; Metabolome ; Metabolomics ; Pharmacogenetics ; Precision Medicine ; methods

Objective To map the complete methylation status of the hMLH1 promoter in sporadic colorectal carcinoma and analyze the relationship between MVPs (methylation variable positions) of hMLH1 promoter and the expression of hMLH1. Methods Methylation status of hMLH1 promoter was measured by bisulfite sequencing. hMLH1 protein expression was detected by immunohistochemistry. Results Out of the 30 sporadic colorectal carcinoma specimens, the hypermethylation of CGIs (CpG islands) 1 was in 6 and that of CGIs 2 in 4. The hMLH1 protein was detected in 15 specimens. Chi square test showed the methylation of CGIs 1 was closely related to loss of hMLH1 protein expression (P0.05). Conclusion In CGIs 1, CpG positions from 1 to 28 are the critical region that could influence the expression of hMLH1.

Acetylcysteine ; pharmacology ; Antioxidants ; pharmacology ; Composite Resins ; toxicity ; Dental Materials ; toxicity ; Fibroblasts ; drug effects ; metabolism ; Gingiva ; cytology ; drug effects ; Humans ; Methacrylates ; toxicity ; Polyethylene Glycols ; toxicity ; Polymethacrylic Acids ; toxicity ; Polymethyl Methacrylate ; toxicity ; Reactive Oxygen Species ; metabolism ; Resins, Synthetic ; toxicity

Objective:To investigate the status of rumination in patients with primary glaucomatous visual field defect and explore the influencing factors.Methods:Totally 267 patients with primary glaucomatous visual field defect were selected via convenience sampling method. Invasive rumination, purpose rumination, and self-management behaviors among different visual field were compared. The main influencing factors of invasive rumination and purpose rumination were analyzed.Results:Total score of rumination in patients with primary glaucomatous visual field defect was (29.90±5.58) points, average item score of self-management behaviors was (2.81±0.31) points. There were no significant difference in invasive rumination, purpose rumination, self-management behaviors among different visual field ( P>0.05). Accidental injury, life adjustment, income of family per mouth and degree of education could explain 30.7% of the total invasive rumination variation; disease management, body function promotion and accidental injury could explain 11.1% of the total purpose rumination variation. Conclusions:Rumination and self-management behaviors in patients with primary glaucomatous visual field were at a lower middle level and middle level respectively. Medical staff should attach importance to assess the invasive rumination among these patients with accidental injury, poor ability of life adjustment, low income of family per mouth and low degree of education. Through lowering the negative experience, changing the cognitive and taking correct self-management behaviors, then prognosis of disease would be improved.

Objective To assess the feasibility of a novel 99Tcm labelled polypeptide analogue for interleukin-11 receptor ( IL11R) imaging in a bone metastases model for prostate cancer. Methods A novel circular polypeptide analogue of IL11 ( c( CGRRAGGSC ) ) was indirectly labeled with 99Tcm and the product was named as 99Tcm-DTPA-IL11 RR. The labeling efficiency, radiochemical purity and stability of the product were measured with paper chromatography and high performance liquid chromatography (HPLC). The biodistribution of 99Tcm-DTPA-IL11RR was investigated in 28 ICR normal mice. The organ radioactivity was measured as percentage activity of injection dose per gram of tissue ( %ID/g). The models of bone metastases from prostate cancer were established at the tibias of BALB/c nude mice bearing human prostate cancer PC-3 cells. The tumor bearing ( n= 5 ) and standard closed fracture nude mice models underwent both 99Tcm-DTPA-IL11RR and 99Tcm-methylene diphosphonate (MDP) scintigraphy study. The images were acquired at 0.5, 1,2, 4, 6, 8, 24 h after intravenous injection of the tracers. The competitive inhibition imaging was perfomed in three tumor bearing mice. One-way variance analysis was used. Results The labeling efficiency was 90.7%. The radiochemical purity of 99Tcm-DTPA-IL11RR in normal saline solution was (99.57 ±0.09)%, (99.29 ±0.18)%, (98.95 ±0.78)%, (98.67 ±0.11)%, (96.53 ±0.91)%, (95.20±0.70)%, (88.38 ±0.22)% and (36.17±1.29)% at room temperature after0, 1,2, 3, 4, 6, 8 and 24 h, respectively. The tracer radiochemical purity in the blood of ICR mice remained over 90% at 37 C for 6 h. The labeling compounds were excreted mainly through kidney. The peak uptake of bone ( ( 1.910 ±0.109) %ID/g) and liver ( (0.366 ±0.030) %ID/g) was at 4 h after injection. In the tumor bearing mice, the uptake of spine marrow and large joints of extremities was mild. The highest uptake at tumor region was at 4 h and persistent at 6-8 h after injection. The tumor to non-tumor ratios (T/NT) were 1.17 ±0.17, 2.20 ±0.29, 3.20 ±0.15, 3.67 ±0.23, 13.61±0.85, 9.45 ±0.37 and 3.33 ±0.30 at 0.5,1, 2, 4, 6, 8 and 24 h, respectively (F=621.54, P＜0.05). In the standard closed fracture models,high uptake of 99Tcm-MDP was shown at the fracture site, with no increased 99Tcm-DTPA-IL11RR uptake noted. The tumor uptake was significantly depressed after a pre-injection of the unlabeled polypeptide analogue. Conclusions The synthesis of 99Tcm-DTPA-IL11RR is stable and the labeling efficiency is high. It may be a potential molecular probe in metastatic bone imaging for prostate cancer.

This paper is to report the study of the pharmacokinetics of a fusion protein TAT-haFGF(14-154) for human acidic fibroblast growth factor and transcriptional activator protein in rat plasma, and the investigation of their penetration across blood-brain barrier in mice and rats, in order to provide a basis for clinical development and treatment of Alzheimer's disease. Enzyme-linked immunosorbent assay (ELISA) was used to determine concentration of TAT-haFGF(14-154) in rat plasma and in mouse brain homogenate; and immunohistochemistry was used to analyze the distribution in brain. The concentration-time curve fitted two-compartment open model which was linear kinetics elimination after a single intravenous injection of TAT-haFGF(14-154) in rat at the dose of 300 microg x kg(-1). The half life time was 0.049 +/- 0.03 h for distribution phase and 0.55 +/- 0.05 h for elimination phase, and the weight was 1/C2. The result showed that TAT-haFGF(14-154) could be detected in the brain by ELISA and immunohistochemistry, the elimination of TAT-haFGF(14-154) in rat was swift, and TAT-haFGF(14-154) could penetrate across the blood-brain barrier, distribute in pallium and hippocampus and locate in the nucleus.

There are reports about the chemical compounds of Ciwujia herbs, but with no study report about the chemical material basis of Ciwujia injection (CWJI). In this study, LC-MS(n) and LC-Q-TOF-MS techniques were adopted for a qualitative analysis on phenylpropanoids in CWJI. The Ultmate XB-C18 column (4.6 mm x 250 mm, 5 microm) was adopted and eluted with the mobile phase of 0.5% formic acid-water and acetonitrile, with the flow rate at 0.8 mL x min(-1) and the column temperature at 20 degrees C. Based on the data of high-resolution and multi-stage MS, control products and literatures, altogether 54 phenylpropanoids were identified in Ciwujia Injection, including 34 phenylpropanoids, 16 ligans and 4 coumarins. Among them, 28 were reported for the first time in Ciwujia, and 14 compound structures were identified in comparison with the control products. The method established in this study could be used to simply and rapidly identify phenylpropanoids in CWJI. The findings provide scientific data for defining the chemical material basis of CWJI.
Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Eleutherococcus ; chemistry ; Mass Spectrometry ; methods ; Molecular Structure

OBJECTIVESTo analyze the survival rate of nasopharyngeal carcinoma (NPC) and to evaluate the effect of intervention in this high risk population of NPC.

METHODSBased on the cancer and vital registry systems, the follow-up data of 1761 NPC cases were collected. The measures of survival include 5-year, 10-year survival rate and median survival duration. Cox model was used to screen the independent prognosis factors.

RESULTSThe 5-year and 10-year survival rates of NPC cases in Sihui were 50.62% and 37.01%, and the median survival duration was 5.05 years. The survival rate of NPC cases diagnosed after 1993 was 58.8%, which was higher than that of cases diagnosed before 1993 (43.3%). Other prognosis factors included gender, age, clinical stage and diagnostic hospital.

CONCLUSIONThere is a significant improvement of NPC survival in Sihui. That is mainly related to the improvement of NPC treatment. However, it needs to a long time observation to see a mortality reduction of NPC.

Adult ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; epidemiology ; mortality ; Prognosis ; Proportional Hazards Models ; Survival Analysis ; Survival Rate

Objective To investigate the role of CD4+CD25+Foxp3 regulatory T cells in chronicity of hepatitis B and viral clearance of hepatitis B virus(HBV).Methods Nineteen patients with chronic active hepatitis B(CAH).21 HBV carriers(AsC)and 12 patients with resolved HBV infection and 1 5 healthy controls were enrolled.The frequency and phenotype of peripheral CD4+CD25+Foxp3+ T cells were detected by flow cytometry.CD4+CD25+T cells were sorted by magnetic-activated cell sorting(MACS)assay.Level of Foxp3 mRNA in CD4+CD25+T cells was examined by real time polymerase chain reaction(PCR)assay.The data were analyzed by one-way ANoVA or nonparametric statistics.Results Both frequencies of CD4+CD25+Foxp3+T cells and levels of Foxp3 mRNA in CD4+CD25+T ceils in patients with CAH or AsC were significantly higher than those in healthy controls Or resolved HBV infection(F=6.8,F=3.72,respectively;both P<0.05).Accumulation of Foxp3+T cells in liver tissue of CAH patients was higher than that of healthy controls,while that in AsC was lower than CAH.The frequency of CD4+CD25+Foxp3+T cells of hepatitis B e antigen(HBeAg)positive patients(including CAH and AsC)was significantly higher than that of HBeAg negative patients(t=2.3,P<0.05),and that of antFHBe negative patients were significantly higher than anti-HBe positive patients(t=2.4,P<0.05).Furthermore,the frequency of CD4+CD25+Foxp3 regulatory T cells was positively correlated with serum HBV DNA level of patients with chronic hepatitis B(r=0.56,P<0.01).Conclusion The findings have important implication in the understanding of the role of CD4'CD25'regulatory T cells in chronicity and viral clearance in HBV infection.